1. Field of the Invention
The present invention relates to a microdosing device and to a method for operating the same.
2. Description of Prior Art
Precise dosing of extremely small volumes of liquid in the range between 0.01 .mu.l and 1 .mu.l is of great and decisive importance e.g. in the fields of biotechnology, DNA analytical chemistry and combinatorial chemistry. According to the prior art, dispensers or pipettes are predominantly used for dosing small volumes. The volume to be dosed is in these cases displaced either directly, by a so-called piston-type direct displacement, or via an intermediate air cushion. In this respect, reference is made e.g. to the article "Pipettieren und Dispensieren", A. Jahns, Fachzeit-schrift der Technischen Assistenten in der Medizin, volume 8 (1993), No. 12, pp. 116-1172, Umschau Zeitschriftenverlag.
Air-cushion pipettes are suitable for dosing volumes between 0.01 .mu.l and 5 ml, accuracies of .+-.2-3% being achieved when the volumes exceed 1 .mu.l. In the case of smaller volumes, however, only accuracies of approx. .+-.10% are achieved due to surface effects at the tip of the pipette. The limited dosing accuracy in the case of smaller volumes is predominantly due to the fact that the tip of the pipette or dispenser must be immersed in the medium to be dosed, whereby the dosing amount is influenced by effects such as surface tension, wetting and hydrostatic pressure. In order to avoid these problems as well as the risk of carrying over media due to immersion, a dosing system should be based on the discharge of the dosed volume in a free jet. Direct-diplacement dispensing devices offer this additional advantage, but only in the case of volumes of approx. 10 .mu.l and more.
Known systems discharging very small volumes of liquid in a free jet are ink-jet printheads. Ink-jet printheads are known which are based on two fundamentally different principles, viz. those which are effective making use of thermal transducers and those which are effective making use of piezoelectric transducers. In this respect, reference is made to the publications N. Schwesinger: "Planarer Tintenstrahldruckkopf". F&M, 11-12; pp. 456-460; 1993; H. Bentin, M. Doering, W. Radtke, U. Rothgordt: "Physical Properties of Micro-Planar Ink-Drop Generators". J. Imaging Technology, 3; pp. 152-155; 1986; and Wolfgang Wehl; Tintendrucktechnologie; Paradigma und Motor der Mikrosystemtechnik; Feinwerktechnik & Me.beta.technik; Teil 1 in Ausgabe 6/95, Teil 2 in Ausgabe 9/95.
When printheads operating according to the "drop-on-demand" principle are used, a small ink drop is flung in a free jet onto a paper after the application of a voltage pulse. A typical drop diameter is approx. 60 .mu.m, i.e. the volume is approx. 0.0001 .mu.l. Normally, these printheads are, however, only adapted to be used in combination with special inks. Media which are used e.g. in the field of biotechnology are in most cases extremely different from these inks as far as viscosity and surface tension are concerned. The viscosity and the surface tension are, however, factors which substantially influence the size of the drops and, consequently, the volume dosed. Furthermore, generation of drops is only possible in a very limited viscosity range. The volume of the individual drops can, moreover, only be modified in a very restricted range by modifying the control pulses.
Furthermore, dosing systems are known, which are also capable of generating drops in the case of media having strongly different viscosities. Such a system is described e.g. in the publication "Mikrodosierung", company publication of the firm of microdrop GmbH, Norderstedt, 1995. As in the case of ink-jet printheads, the drop volume produced in these systems is determined mainly by the size of the nozzle diameter. Only to a very limited extent can it also be influenced by the electric control of the actuator. As in the case of ink-jet printheads, the process of drop interruption at the nozzle depends, however, on the physical properties, i.e. the viscosity, the surface tension, etc. of the media to be dosed. The exact size of the drops is therefore again strongly media-dependent. The dosing of a desired volume, which ranges between 0.1 .mu.l and 1 .mu.l in most cases, is based the counting of individual drops of the same size. The typical volume of an individual drop is smaller than 0.001 .mu.l. Since the volume errors of the individual drops will, however, accumulate in this process, the dosing accuracy is strongly limited.
In order to permit an increase of this dosing accuracy, complicated systems are necessary. An image processor can, for example, be used by means of which the size of the individual drops can be determined and the number of drops required can be calculated during the dosing process. According to an alternative method of increasing the dosing accuracy, a fluorescent substance can be admixed to the medium to be dosed. In the case of this alternative method, the dosing process will be finished when the intensity of the fluorescent signal has reached the set value. It is, however, apparent that the above-mentioned methods of increasing the dosing accuracy are both very complicated and expensive.
EP-A-0439327 describes a control system for a micropump, which is adapted to be used e.g. in a dosing device. The control system selectively controls the generation of drive pulses so as to control the discharge of fluid through the pump. According to the known control system, fluctuations of potential of the piezoelectric driver element of the micropump are detected so as to find out whether or not the pump operates properly so that operation of the pump can be stopped and the micropump can be replaced, if necessary.
U.S. Pat. No. 5,205,819 discloses an infusion pump for dosing liquids, e.g. when liquids are being infused into the human body. The disclosed infusion pump comprises a pressure chamber which is partly delimited by a membrane. A piezo-electric component is provided for actuating the membrane. The pressure chamber is adapted to be connected to a liquid reservoir via an inlet line and to an outlet opening via an outlet line. A control unit is provided for controlling the piezoelectric component; the infusion pump can additionally be provided with detection electrodes providing signals which indicate the degree of bending of the membrane. These detection electrodes serve, on the one hand, the purpose of indicating error conditions caused by air bubbles in the pump chamber or by a clogged outlet line. During normal operation, the detection electrodes may, on the other hand, serve the purpose of providing an output signal representing a measure of the liquid volume dosed in the case of each actuation of the membrane. In order to provide a pre-determined flow rate, the control unit is programmed for adjusting the pulse frequency for the actuation of the piezoelectric component in dependence upon the signal amplitude of the output signal of the detection electrodes. The known infusion pump is driven by a sequence of pulses consisting each of positive and negative pulses having the same amplitude and duration, the frequency of the sequence of pulses being controlled in accordance with the necessary flow rate.